Wu J N, Tiffany-Castiglioni E
Department of Veterinary Anatomy, Texas A&M University, College Station 77843.
In Vitro Cell Dev Biol. 1987 Nov;23(11):765-74. doi: 10.1007/BF02623678.
Time- and dose-dependent toxic effects of lead (Pb) acetate on astroglia, oligodendroglia, and meningeal fibroblasts cultured from immature rat brain were measured. Cultures were exposed for 3 d to Pb (1, 10, and 100 microM) and then examined immediately (Day 0) or 3 or 10 d after Pb treatment was discontinued. The percentages of astroglia and fibroblasts excluding dye were unaffected by Pb, whereas the percentage of oligodendroglia excluding dye decreased significantly (P less than 0.01) at all time points after exposure to 100 microM Pb. Lead (100 microM) also reduced the total cell numbers of astroglia, oligodendroglia, and meningeal fibroblasts. Amino acid incorporation into protein by oligodendroglia was stimulated after exposure to 100 microM Pb at all time points and also by 1 and 10 microM on Day 3. Incorporation was stimulated in astroglia only on Day 0 by 10 and 100 microM. Hydrocortisone-stimulated glycerolphosphate dehydrogenase (GPDH) activity was assayed in oligodendroglia cultures. A significant decrease in specific activity was seen after a 4-d exposure to lead. Because oligodendroglia are responsible for myelin synthesis in the central nervous system, and GPDH may synthesize a precursor for myelin lipid synthesis, it was proposed that the hypomyelination observed in lead-intoxicated neonatal rats may result partially from a primary toxic effect on oligodendroglia. GPDH activity was not inhibited by Pb in mixed glial cultures containing both astroglia and oligodendroglia. This result suggests that astroglia in culture have the ability to delay the lead-induced inhibition of oligodendroglial GPDH activity and supports the hypothesis that astroglia in culture serve a protective function.
测定了醋酸铅（Pb）对从新生大鼠脑分离培养的星形胶质细胞、少突胶质细胞和脑膜成纤维细胞的时间和剂量依赖性毒性作用。将培养物暴露于Pb（1、10和100微摩尔）3天，然后在Pb处理停止后立即（第0天）、3天或10天进行检查。排除染料的星形胶质细胞和成纤维细胞的百分比不受Pb影响，而暴露于100微摩尔Pb后，在所有时间点排除染料的少突胶质细胞的百分比均显著降低（P<0.01）。100微摩尔的Pb也减少了星形胶质细胞、少突胶质细胞和脑膜成纤维细胞的总细胞数。在所有时间点，暴露于100微摩尔Pb后，少突胶质细胞中氨基酸掺入蛋白质的过程均受到刺激，在第3天，1和10微摩尔的Pb也有此作用。仅在第0天，10和100微摩尔的Pb刺激星形胶质细胞中的掺入。在少突胶质细胞培养物中测定了氢化可的松刺激的甘油磷酸脱氢酶（GPDH）活性。暴露于铅4天后，比活性显著降低。由于少突胶质细胞负责中枢神经系统中的髓鞘合成，且GPDH可能合成髓鞘脂质合成的前体，因此有人提出，在铅中毒新生大鼠中观察到的髓鞘形成减少可能部分是由于对少突胶质细胞的原发性毒性作用。在同时含有星形胶质细胞和少突胶质细胞的混合胶质细胞培养物中，GPDH活性未被Pb抑制。这一结果表明，培养中的星形胶质细胞有能力延迟铅诱导的少突胶质细胞GPDH活性抑制，并支持培养中的星形胶质细胞具有保护功能这一假说。
